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PubMed1976

Effects of xipamide and triamterene - alone or in combination - on electrolyte excretion in the rat.

The effects of X and T in different doses alone or in combination on renal sodium and potassium excretion were examined in conscious rats. In acute experiments, the combination of both diuretics produced an approximately additive effect on sodium excretion. Addition of T to X in different dose relations (X:T = 1:0.5, 1:1 or 1:1.5) prevented the X-induced potassium loss. These effects were more pronounced at the highest dose of T; the difference to the other combinations, however, was small. In chronic experiments, when the diuretics were administered daily for 13 days, both combinations (X:T = 1:1 and X:T = 1:1.5) resulted in a nearly equilibrated potassium balance at the end of this period. In shorter intervals, however, sometimes considerable oscillations in potassium excretion occured.

Animals↗

PubMed1988

Erythrocyte and leucocyte sodium and potassium transport systems during long-term diuretic administration in men.

The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The intra-erythrocyte and intra-leucocyte Na+ concentration was increased by 11 and 7%, respectively, during xipamide administration, while the intracellular K+ concentration was decreased by 3 and 4%, respectively. No significant effect of xipamide could however be demonstrated on the ouabain-sensitive, bumetanide-sensitive or ouabain-bumetanide-resistant 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+-Li+ countertransport was also not changed in the xipamide-treated subjects. Our data suggest that the increased intracellular Na+ concentration and the decreased K+ concentration in red and white blood cells of xipamide-treated subjects cannot be attributed to changes in the activity of the Na+ pump, the Na+-K+ cotransport or Na+-Li+ countertransport system or to changes in the number of active Na+ pump units.

Adult↗

PubMed1994

Liver cirrhosis with ascites: pathogenesis of resistance to diuretics and long-term efficacy and safety of torasemide.

In a prospective randomized short-term study, the efficacy and safety of xipamide and a combination of spironolactone and furosemide were compared in the treatment of hepatic cirrhotic ascites. Twenty-two patients were randomized to either xipamide, 20 mg/day (group I), or spironolactone, 200 mg/day, combined with furosemide, 40 mg on alternate days (group II). During the first 4 days of treatment, adequate diuresis, measured as loss of body weight greater than 1.6 kg, occurred in 7 patients in group I and in 3 in group II. In the latter group, another 4 patients responded satisfactorily after a further 4 days of treatment. Four patients in group I who failed to respond to xipamide with an adequate loss of body weight were subsequently treated with the spironolactone-furosemide combination, but only one responded. Two patients in group II who failed to respond to the combination of spironolactone and furosemide also failed to respond to xipamide. In both groups, a positive diuretic response occurred only when the pretreatment fractional sodium excretion exceeded 0.2%. Diuretic resistance was overcome only by additional treatments which reduced proximal tubular sodium reabsorption. Xipamide commonly induced hypokalaemia; in contrast hyperkalaemia was seen following treatment with the spironolactone-furosemide combination. Renal function remained stable in all patients during both diuretic treatments. An open ongoing 6-month trial of torasemide, 10-40 mg/day, in combination with spironolactone, 50-400 mg/day, has also been undertaken in 117 patients with cirrhotic ascites who showed inadequate responses to salt and water restriction and spironolactone alone. Twenty-seven patients have been withdrawn from the study, 9 for the complications of hepatic coma, bleeding oesophageal varices, or hyponatraemia. Twenty-two patients are still being treated and 68 have completed the trial on a mean dose of torasemide, 15 mg/day. Body weight was reduced by a mean of 2.3 kg at 6 weeks, 2.6 kg at 14 weeks and 3.2 kg after 6 months. Loss of body weight was primarily associated with reduction of ascites and secondarily with reduction of peripheral oedema. There were no untoward adverse reactions with torasemide, and no significant changes in serum electrolytes, liver, renal, or haematological variables.

Ascites↗

PubMed1986

Liver carbonic anhydrase and urea synthesis. The effect of diuretics.

In isolated perfused rat liver, urea synthesis is rapid and reversibly inhibited not only by the well-known carbonic anhydrase inhibitors acetazolamide, methazolamide and ethoxzolamide, but also by diuretics, like xipamide, mefruside, chlortalidone, and chlorothiazide. Furosemide was without effect. Similar to findings with isolated perfused rat liver, acetazolamide inhibits urea synthesis from ammonium ions in normal and cirrhotic human liver slices. Inhibition of urea synthesis by xipamide and acetazolamide is accompanied by a 70% decrease of the cellular citrulline content and the tissue levels of 2-oxoglutarate and citrate, suggesting a block of urea synthesis at a step prior to citrulline formation. At a constant extracellular pH (7.4), inhibition of urea synthesis by xipamide, mefruside and acetazolamide was overcome by increasing the extracellular concentrations of HCO3- and CO2 to above twice the normal values. This shows that inhibition of urea synthesis by these diuretics is not due to an unspecific inhibition of one of the urea cycle enzymes but is due to an inhibition of mitochondrial carbonic anhydrase and therefore due to an impaired HCO3- provision for mitochondrial carbamoylphosphate synthesis. It is concluded that the activity of mitochondrial carbonic anhydrase is required for urea synthesis also in human liver and that several diuretics impair urea synthesis by inhibition of mitochondrial carbonic anhydrase. The pathophysiological significance of these data is discussed with respect to the development of diuretics-induced hyperammonemia and alkalosis in liver disease.

Acetazolamide↗

PubMed1995

[Effect of 3 hypertensive++ agents on ventricular geometry and function].

BACKGROUND: To assess the prevalence of left ventricular hypertrophy in hypertensive patients referred to an outpatient cardiology unit, and to assess its evolution under antihypertensive treatment. METHODS: One hundred and seven mild to moderate hypertensive patients were randomized to receive either xipamide, verapamil or atenolol. Cross-sectional echocardiography was performed in order to assess left ventricular mass and function. RESULTS: Mean age was 56 years, with a 4:1 female/male ratio. Mean follow-up was 120 days. Left ventricular hypertrophy was very common (65%) and decreased to 54% under antihypertensive treatment. Left ventricular mass decreased from 134.3 g/m2 to 118.1 g/m2 (p < 0.001). Concentric hypertrophy was the most common geometric pattern (42%), decreasing to 30% with treatment. Xipamide decreased ventricular mass by decreasing left ventricular diameters, while verapamil and atenolol decreased left ventricular thickness, mainly in septal wall. Systolic function was not modified during the treatment period. Diastolic function was not modified by xipamide and verapamil, and improved with atenolol. CONCLUSIONS: Left ventricular hypertrophy is very frequent when determined by echocardiography and all three drugs produced regression of left ventricular hypertrophy in a different way with respect to left ventricle geometry, an effect which could have potential therapeutic implications.

Atenolol↗

PubMed1991

[Study of blood pressure response to exertion in essential hypertension. Its modification with anti-hypertensive treatment].

We have studied the effect of atenolol, xipamide, and verapamil in the control of effort tensional response in 54 patients suffering essential hypertension. A first effort test without treatment and a second after a one month treatment randomly assigned were performed in all patients, evaluating the tensional response at 30, 60 and 80 Watts of charge, maximum peak, and after five minutes in recovery. Atenolol significantly reduced (p less than 0.05) systolic arterial pressure and diastolic arterial pressure in every intermediate effort stage, maximum peak and post effort recovery, xipamide, also significantly reduced (p less than 0.05) the systolic hypertensive response at all different levels, however, the diastolic one did not reach any statistic significance. Verapamil at used doses did not modify neither systolic nor diastolic hypertensive response. The beneficial effect of beta-blockers is confirmed although we could not confirm the effect pointed out by other authors regarding calcium antagonists. Tensional control using xipamide was striking although there is some evidence to think that it can have a more important effect in the control than thiazide diuretics or amiloride.

Adult↗

PubMed1990

Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion.

In a randomized prospective study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied. Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function. The remaining 22 patients were randomized to additional treatment with either 20 mg xipamide/day (group I) or 200 mg spironolactone/day combined with 40 mg of furosemide every other day (group II). A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II. In the latter group 7 of 11 patients finally responded after 8 days of treatment. Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion, FENa. The resistance to diuretic treatment can be predicted by a FENa less than 0.2%, and could be overcome by additional strategies known to reduce avid proximal Na reabsorption. Xipamide frequently induced hypokalemia, whereas hyperkalemia was seen following treatment with spironolactone/furosemide. Kidney function remained stable during either diuretic treatment.

Adult↗

PubMedDate not supplied

[The regression of left ventricular hypertrophy following a short antihypertensive treatment].

With the objective of trying to prove the regression of ventricular mass in patients with essential hypertension, with and without left ventricular hypertrophy (LVH), we studied 42 patients of both sexes with echocardiography, measuring the left ventricular mass (LVM), the mean parietal thickness (MPT) and the relative parietal thickness (RPT), before and after one month of random treatment with atenolol, verapamil and xipamide, independently that the blood pressure control was or not satisfactory. We found significant reductions in the MPT with verapamil and atenolol (p = 0.006 and 0.036), although only verapamil induced a significant reduction of the LVM. The RPT did not shown any significant modification, although the tendency was opposed with xipamide and the other two groups, verapamil and atenolol. The factor Adequate control of the blood pressure, with any of the treatments, proved to be helpful in the favorable evolution of the regression. The degree of LVH before treatment does not appear to have any influence in the posterior evolution with the treatment.

Adult↗

PubMed1988

[Photoallergy to Neotri and cross reaction to tenoretic--detection by systemic photoprovocation].

A patient is presented who suffered for 3 years from increasing photosensitivity with chronic eczematous lesions in sun-exposed areas. He had taken one Neotri (triamterene, xipamide) tablet daily for 6 years. After discontinuation of the drug, phototesting and a photopatch test failed to reveal pathological reactions. Eczematous lesions, however, were induced in test areas upon systemic photochallenging with Neotri. One year later, after the antihypertensive medication had been changed from Adalat (nifedipine) to Teneretic (atenolol, chlortalidone) the eczematous photosensitive reaction recurred. Since both xipamide and chlortalidone have a chlorsulfamoyl-substituted aromatic ring in common, it seems that a photoallergic cross-reaction occurred.

Aged↗

PubMed1982

Acute and chronic diuretic-induced alterations in urinary sodium and calcium excretion in the conscious rat.

The acute and chronic (5-day) effects of three low-ceiling diuretics (hydrochlorothiazide, indapamide or xipamide) and two high-ceiling diuretics (furosemide or muzolimine) on urinary volume and electrolyte excretion were examined in the saline-loaded conscious rat. The three low-ceiling agents produced qualitatively similar alterations in both acute and chronic volume and electrolyte excretion patterns. Each of these agents produced an acute disassociation between urinary sodium and calcium excretion and hypocalciuria after chronic administration. It is suggested that indapamide and xipamide, like hydrochlorothiazide, inhibit sodium but not calcium reabsorption in the distal nephron. Acute as well as chronic treatment with either furosemide or muzolimine produced dose-dependent increases in urinary volume and electrolyte excretion. A generally parallel response was observed on sodium and calcium excretion with these agents. It is suggested that muzolimine, like furosemide, inhibits both sodium and calcium reabsorption in the ascending limb of Henle's loop.

Animals↗

PubMed1997

Cell cultures in the investigation of thiazide phototoxicity.

The NHIK 3025 cell line (Norsk Hydro Institutt for Kreftforskning), a human in situ carcinoma of the cervix cell line, was used to investigate the thiazides bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide for their potential phototoxic properties. Cell death following UVA irradiation and dependent on test substance concentration was observed in the presence of all the tested substances except chlortalidone, furosemide, indapamide and xipamide. Bendroflumethiazide was phototoxic at concentrations of 0.05 mM and higher; bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 0.25 mM and higher and butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 0.5 mM and higher.

Benzothiadiazines↗

PubMed2005

Trough levels of mycophenolic acid and its glucuronidated metabolite in renal transplant recipients.

OBJECTIVE: The prophylactic use of the immunosuppressant prodrug, mycophenolate mofetil (MMF) to prevent graft rejection in renal transplant patients is continuing to increase. We measured trough levels of the active metabolite, mycophenolic acid (MPA) and its inactive glucuronide (MPAG) in renal recipients with the aim of characterizing individual variability and of ascertaining factors influencing trough levels, in particular the effect of differences in renal function and the effect of drugs given concurrently. METHODS: Laboratory and clinical data obtained in 35 renal recipients treated with triple therapy (MMF, cyclosporin A (CsA), steroids) were included in this retrospective study. Trough levels of MPA and MPAG were obtained after transplantation and up to 16 months post transplantation where the mean observation period was 5.7 months. Plasma levels were measured using a validated HPLC assay. RESULTS: A total of 212 plasma concentrations of MPA and 209 of MPAG were measured. There was considerable intra- and interindividual variability in MPA and MPAG trough levels especially in the early post-transplantation phase. At a fixed dose of 2 g/d MMF, the mean MPA level during the first 30 days averaged 1.46 +/- 1.31 microg/ml vs. 1.87 +/- 0.89 microg/ml after 30 days and later (p = 0.130) and the mean MPAG concentration averaged 188.1 = 142.8 [microg/ml vs. 98.09 +/- 52.4 microlg/ml (p 0.003). The MPAG levels were positively correlated with the serum creatinine concentrations (r = 0.815, p < 0.001), and in the case of MPA there was a correlation with the serum protein concentrations (r = 0.258, p = 0.001). Concomitant drug treatment using CsA, steroids and furosemide were without effect of the measured plasma concentrations, but in the case of xipamide (+) and diltiazem (-) an effect on MPA and MPAG levels and a co-effect depending on the serum creatinine could not be excluded. Neither CsA trough levels nor hemoglobin levels were related to MPA and MPAG trough levels. CONCLUSIONS: The data of this study demonstrate that there is substantial individual variability in the trough levels of MPA and MPAG after renal transplantation which may be associated with the functional status of the graft and the serum protein level. Whether comedication with xipamide and diltiazem affects the plasma levels of MPA and MPAG remains to be clarified in further investigations.

Adolescent↗

PubMed1989

[Effects of antihypertensive treatment on the relaxation of the left ventricle in hypertensive patients].

To increase our understanding of the interaction between anti-hypertensive drug therapy and left ventricular filling, 23 hypertensive patients (DBP 100 +/- 4 mmHg) had their myocardial mass measured and underwent gamma-angiography (determination of maximum volume of filling, MVF, end-diastolic volume/s-1, and the maximum time for filling, MTF, ms) before and after therapy with propranolol (100 mg/d), captopril (50 mg/d), nitrendipine (28 mg/day) or xipamide (20 mg/d). Blood pressure was recorded in the four treatment groups, and myocardial mass regressed only in those treated with propranolol or nitrendipine. Only the latter drug acts simultaneously on MVF (2.19 +/- 0.22 vs 2.47 +/- 0.43 EDV/s -1) and MTF (221 +/- 21 vs 192 +/- 20 ms) significantly (p less than 0.05). Xipamide only improved MTF (228 +/- 28 vs 209 +/- 20 ms; p less than 0.05). These data compared to those of the literature demonstrate the variability in the antihypertensive effects on ventricular filling, while its improvement may be proposed as a usual objective in treatment of hypertensive disease.

Adult↗

PubMed1997

Studies on the phototoxic effects of oral antidiabetics and diuretics.

A number of sulphonamide derived oral antidiabetics (chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide) and diuretics (bemetizide, bendroflumethiazide, benzylhydrochlorothaizide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide) were investigated for phototoxicity in a cell culture model. Cell death dependent on UVA fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydroxhlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at 5 x 10(-5) mol/l and higher concentrations, bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at 2.5 x 10(-4) mol/l and higher concentrations, and the oral antidiabetics glibenclamide and gliquidone as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at 5 x 10(-4) mol/l and higher concentrations. The oral antidiabetics chlorpropamide, glipizide, glymidine, tolazamide and tolbutamide as well as the diuretics chlortalidone, furosemide, indapamide and xipamide did not induce phototoxicity in this assay.

Carcinoma in Situ↗

PubMed2003

Effect of the location of hydrogen abstraction on the fragmentation of diuretics in negative electrospray ionization mass spectrometry.

The diuretic agents bumetanide, xipamide, indapamide, and related compounds were investigated in order to determine the effect of different ionization sites on their collisionally activated dissociation and the corresponding fragmentation pathways. Therefore, analytes were selectively alkylated, and structural analogues as well as deuterium labeled compounds synthesized, which contain a reduced number of ionizable hydrogen atoms. Thus, specific hydrogen abstractions and their correlated dissociation routes of the negatively charged molecules were eliminated, providing evidence for the influence of the location of ionization on product ion spectra. Fragment ions such as m/z 78 indicate ionization at the commonly present sulfamoyl residue of diuretics but does not exclude additional ionization sites. Product ion spectra of the investigated diuretic agents proved to be composed by fragmentations initiated from different hydrogen abstractions. Moreover, the generation of radical anions by collision-activated dissociation of even-electron precursor ions was observed, the generation of which is discussed by proposed fragmentation pathways.

Bumetanide↗

PubMed2004

Experimental design optimization of a capillary zone electrophoresis method for the screening of several diuretics and ACE inhibitors.

Experimental design methodologies are applied to the development of a capillary zone electrophoretic method for the separation of the angiotensin-converting enzyme inhibitor enalapril and its derivative enalaprilat and the diuretics xipamide and hydrochlorothiazide. The effects of pH, buffer concentration, proportion of boric acid in the mixed boric acid-potassium dihydrogen phosphate background electrolyte, temperature, applied voltage, and percentage of organic modifier are studied. Critical factors are identified in a screening design (a 2(6-2) fractional factorial design), and afterwards, optimal conditions for the separation are reached by means of an optimization design (a 2(2) + 2 x 2 + k central composite design). The studied response is the resolution between peaks. The four studied compounds can be separated in less than 3.5 min using an electrolyte of 20mM boric acid-potassium dihydrogen phosphate (75:25, v/v) with 5% MeOH adjusted to pH 8.0 with KOH, at a potential of 30 kV. The detection wavelength and temperature are 206 nm and 35 degrees C, respectively.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1980

A patient compliance comparative study of three diuretics in the treatment of oedema.

Diurexan (xipamide) 40 mg daily was substituted for Navidrex-K (cyclopenthiazide 0.25 mg plus potassium 600 mg) or Moduretic (amiloride hydrochloride 5 mg plus hydrochlorthiazide 50 mg) in nineteen patients with oedema of cardiac origin. Comparative efficacy and patient acceptability were examined over a 4-week treatment period. In six patients their oedema was resolved and in a further seven their oedema was markedly reduced (six patients had no overt oedema pre-trial). The body-weight of nine patients decreased by an average of 1.4 kg whilst in seven patients it remained static and in three patients it increased by an average of 1.8 kg. Thirteen of the patients preferred Diurexan at the end of the 4-week trial period, four patients had no preference and two patients preferred their previous treatment.

Adult↗

PubMed1990

[The prevalence of arrhythmias and repolarization changes in patients with mild or moderate essential hypertension undergoing an exercise test. Their variations with different antihypertensive treatments].

42 mild and moderate hypertensive patients treated with Verapamil, Atenolol and Xipamide were studied. Exercise tests (ET) were performed at the onset and after a month of therapy, in order to detect arrhythmias and repolarization change prevalence of ventricular arrhythmias (VA) was 23.7% and 11.9% for supraventricular arrhythmias (SVA). 45.2% of the exercise tests were considered positive, with a significant correlation with maximum pressure peak. Patients with left ventricular hypertrophy (LVH) showed a significant increase in VA and +ET prevalence (42.1% and 63.2%). After treatment, the prevalence for VA registered a slight decrease and an increase for SVA; these differences not being considered significant. +ET showed a significant decrease in all patients, as well as in those with previous LVH (21.4%, 26.3%). Only atenolol produced a significant decrease in the +ET of patients with previous LVH (75% to 12.5%).

Adult↗